Clinical Trial of Hydrogen-Rich Celsior Solution Applied in Aging DBD Liver/Kidney Transplantation

Phase 3

• Conditions: Evidence of Liver Transplantation
• Interventions: Drug: Hydrogen-Rich Celsior Solution

• Registration Number: NCT02613195
• Lead Sponsor: RenJi Hospital

Brief Summary

The purpose of this study is to investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/kidney transplantation.

Detailed Description

The organ shortage has been rising to impede the development of organ transplantation.To find a solution, transplantation center is working on the application of marginal grafted liver or renal, especially the aging grafts. The most common inducement of organ dysfunction during the perioperation is liver/renal ischemia-reperfusion (I/R) injury, caused by the generation of cytotoxic oxygen radicals. Hydrogen gas is a kind of reducing gas, which has been reported to display antioxidant properties and protective effects against organ dysfunction induced by various I/R injuries. Investigators will investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/ kidney transplantation.

Study Timeline

• Status Verified: 2015-10
• Study First Submitted: 2015-10-24
• Study First Submitted QC: 2015-11-20
• Last Update Submitted: 2015-11-20
• Study First Posted: 2015-11-24
• Last Update Posted: 2015-11-24
• Study Start: 2016-01
• Primary Completion: 2017-02
• Study Completion: 2017-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Donors:

1. Age of the donor ≥60 yrs.
2. The donor has no historical records of drug abuse, alcoholic abuse, homosexual,or drug addiction, etc.
3. Evaluate infections and infectious disease of the donor.
4. History of malignant tumor;
5. History of hypertension, diabetes, hemophilia, or other anticoagulant disease,kidney donor should not have a history of kidney disease.
6. Daily urine volume is approximately normal.
7. Donor should be subjected to physical examination by medical doctor of OPO stuff before donation; the OPO stuff should realize whether the potential donor has infected lesion or not, such as abscess, ulcer, lymphadenectasis， etc., and evaluate infectious risk of recipient post-operationally.
8. OPO stuff should realize the dynamic change of body temperature, as well as various intensive care parameters of the potential donor, it shall be very important to be sure whether the potential donor has pulmonary/ systemic infections or not,especially for whom has longer ICU duration (> 7 Days).
9. The potential donor should has a systolic blood pressure ≥ 50 mm Hg (1mmHg=0.133 kPa) and arterial SaO > 80%.
10. Liver Biochemistry: alanine aminotransferase (ALT) ≤ 6ULN, total bilirubin (TBil) ≤ 50umol/L;Kidney Biochemistry: serum creatinine (sCre) ≤ 2ULN;
11. Negative anti-HIV antibody;
12. Negative bacterial and fungal culture in blood;
13. Ultrasonic diagnosis of fatty liver, trauma, hematoma, lithiasis, etc., as well as size of both kidney, hydronephrosis, nephrolithiasis, etc. if possible.
14. Graft liver should be soft, normal color and even, no tumor or other abnormity;steatosis ≤ 30% by liver biopsy.Graft kidneys should have complete renal capsule with no congestion or bleeding;proximal tubular necrosis ≤ 50%, without obvious structural damage.Organ (liver and kidney) cold ischemia time (CIT) is determined as the time duration from cold preservation of organs to transplant re-perfusion. CIT of aging DBD liver and kidney graft should be ≤ 10 and16 hours, respectively.

Recipients：

1. Aged between 18-65 years old
2. MELD score ≤25,BMI≤25
3. Patients with tumor,the expected lifetime≥6 months
4. Agree to anticipate the trial and sign the informed consent

Exclusion Criteria

• Donor's age < 60 yrs;
• The donor has historical records of drug abuse, alcoholic abuse, homosexual, or drug addiction, etc.
• The donor is HIV infected, or has severe infection, or positive bacterial and/ or fungal culture results;
• Uncontrollable hypertension, diabetics;
• Malignant tumor;
• Unstable hemodynamic response or SaO status, such as systolic pressure <50 mm Hg (1mmHg=0.133 kPa) , or arterial SaO<80%.
• Liver Biochemistry: alanine aminotransferase (ALT)>6ULN, total bilirubin (TBil)>50umol/L;
• Graft liver has a steatosis >30%, or graft kidney has a proximal tubular necrosis>50% or obvious glomerular sclerosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydrogen-rich Celsior solution	Hydrogen-Rich Celsior Solution	Using aging liver grafts（≥60 years old)，lavaged and cold stored with hydrogen-rich Celsior solution for 2-4 hours.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in glomerular filtration rate（GFR）	up to 6 months
Change From Baseline in creatinine	up to 6 months
Change From Baseline in Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT)	up to 6 months
Change From Baseline in direct bilirubin(DBil)/total bilirubin(TBil)	up to 6 months

Secondary Outcome Measures

Name	Time	Method
Mitochondrial function index of hepatocyte/nephrocyte during surgery	during surgery
Pathological score of liver/kidney preservation injury during surgery	during surgery
Early graft function incidence	baseline and 6 months
postoperative complications	up to 6 months
The total incidence of adverse events/incidence of severe adverse events	up to 6 months
Graft dysfunction incidence	baseline and 6 months
Recipient survival	baseline and 6 months

Trial Locations

Locations (2)

Ren Ji Hospital; 🇨🇳 Shanghai, Shanghai, China

Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; 🇨🇳 Shanghai, China